Malignant paraganglioma and somatotropinoma in a patient with germline SDHB mutation-genetic and clinical features

Abstract

Background: Pituitary adenomas and paragangliomas/pheocromocytomas are rare endocrine tumours, which can be sporadic or familial. During many years their coexistence in the same individual was considered a coincidental finding. However, an association between these two entities was recently demonstrated, with the possible involvement of SDHx genes.

Case report: We describe a 57-year-old female patient, who was under surveillance since 1997 for a malignant paraganglioma with vertebral bone metastasis, and harboured a germline frameshift mutation in exon 6 of SDHB gene [c.587-591DelC]. Seventeen years later, she was diagnosed with acromegaly and underwent transesphenoidal endoscopic resection of a somatotropinoma. Three months after surgery she started treatment with lanreotide for residual disease. Despite initial good response, she developed resistance to first generation of somatostatin analogues and treatment had to be switched to pegvisomant. In the immunohistochemical staining, the pituitary adenoma was positive for SDHA expression, while SDHB showed an heterogeneous staining pattern, with areas markedly positive and others with positive and negative cells.

Conclusions: Our findings provide useful data for understanding the link between paragangliomas/pheocromocytomas and somatotropinomas. While we confirm the well-established link between SDHB mutations and paragangliomas/pheocromocytomas, particularly with malignant paragangliomas, the preservation-at least partially-of SDHB expression in the somatotropinoma tissue does not allow drawing definite conclusions about the involvement of the SDHB mutation in pituitary adenoma.

Keywords: Paraganglioma; Resistance to Somatostatin Analogs; SDHB gene; Somatotropinoma.